9-37436635-CCTCTCTCTCT-CCTCTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_012203.2(GRHPR):c.866-12_866-9del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,516,864 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 28)
  • Exomes 𝑓: 0.00060 (5 hom.)
• Consequence: GRHPR NM_012203.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.455

Genes affected

GRHPR (HGNC:4570): (glyoxylate and hydroxypyruvate reductase) This gene encodes an enzyme with hydroxypyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase enzymatic activities. The enzyme has widespread tissue expression and has a role in metabolism. Type II hyperoxaluria is caused by mutations in this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-37436635-CCTCT-C is Benign according to our data. Variant chr9-37436635-CCTCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 2731099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00354 (535/151140) while in subpopulation AFR AF= 0.0114 (470/41268). AF 95% confidence interval is 0.0105. There are 5 homozygotes in gnomad4. There are 267 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRHPR	NM_012203.2	c.866-12_866-9del		intron_variant		ENST00000318158.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRHPR	ENST00000318158.11	c.866-12_866-9del		intron_variant		1	NM_012203.2	P1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 536 AN: 151034 Hom.: 5 Cov.: 28

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000340

Gnomad OTH AF: 0.00338

GnomAD4 exome AF: 0.000601 AC: 821 AN: 1365724 Hom.: 5 AF XY: 0.000544 AC XY: 370 AN XY: 680136

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.00153

Gnomad4 ASJ exome AF: 0.00395

Gnomad4 EAS exome AF: 0.000111

Gnomad4 SAS exome AF: 0.000198

Gnomad4 FIN exome AF: 0.000240

Gnomad4 NFE exome AF: 0.000151

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome AF: 0.00354 AC: 535 AN: 151140 Hom.: 5 Cov.: 28 AF XY: 0.00362 AC XY: 267 AN XY: 73808

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.000194

Gnomad4 NFE AF: 0.000340

Gnomad4 OTH AF: 0.00335

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34302950; hg19: chr9-37436632;